PB2064: THE COMPLETE STUDY: A SINGLE ARM, MULTICENTER OBSERVATIONAL STUDY TO EVALUATE EFFECTIVENESS OF PEGCETACOPLAN UNDER REAL WORLD CONDITIONS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
Authors: Régis Peffault de Latour, Jeff Szer, Austin Kulasekararaj, Anna Gaya, Simona Sica, Matthias Nölte, Regina Horneff, Lethagen Stefan
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by complement-mediated hemolysis with resultant thrombosis risk and a substantial patient symptom burden. Complement C5 inhibitors (C5i) have improved outcomes by reducing intravascular hemolysis (IVH). Extravascular hemolysis (EVH) continues or becomes evident under C5i treatment, with anemia persisting or recurring in >80% of patients, which may lead to transfusion dependence, fatigue, and impaired quality of life (QoL) (Risitano et al. Blood 2009; Panse et al. Eur J Haematol 2022). Pegcetacoplan is a novel complement C3 inhibitor (C3i) that controls EVH and IVH. In the phase 3 PEGASUS (NCT03500549) trial of patients with persistent anemia despite eculizumab therapy, pegcetacoplan showed head-to-head superiority in mean hemoglobin (Hb) change vs. eculizumab. Pegcetacoplan also demonstrated rapid and sustained Hb stabilization in complement inhibitor-naïve patients in the phase 3 PRINCE (NCT04085601) trial. Pegcetacoplan was approved by the EMA in 2021 for adult PNH patients who are anemic after C5i treatment for ≥3 months. There is currently a need for real-world data on pegcetacoplan usage and effectiveness in the PNH community. Aims: To describe real-world effectiveness of pegcetacoplan in the treatment of adult patients with PNH (Figure 1). QoL and health care resource use, physician and patient satisfaction with the treatment will also be assessed. Methods: COMPLETE is a Phase 4, multicenter, observational study aiming for 200 patients across 70 sites in Europe, the Middle East, Canada, and Australia. The study will include patients (≥18 years) with documented PNH diagnosis who started pegcetacoplan ≤12 months prior enrollment or are prescribed pegcetacoplan at enrollment. The decision to start treatment will be made by the treating physician and independent from the decision to include the patient in the study. Patients who initiated current pegcetacoplan treatment in an interventional trial, those enrolled in a concurrent interventional study or receiving an investigational product ≤3 months prior to start of current pegcetacoplan treatment, will be excluded. The primary endpoint is change in observed Hb level from initiation of pegcetacoplan treatment to 6 months. Changes in lactate dehydrogenase, absolute reticulocyte count, bilirubin, haptoglobin, and ferritin levels will also be assessed from treatment initiation to 6 months. These parameters will be determined at 6-month intervals until the end of study. The alleviation of ongoing anemia will be evaluated by assessing the achievement of Hb ≥12 g/dL and increase in Hb of ≥2 g/dL, likewise at 6-month intervals. Lastly, endpoints reflective of acute events will be examined, including annualized number and units of red blood cell transfusions and acute hemolytic events requiring additional intervention. Adverse events will be collected throughout the study. QoL will be evaluated via patient reported outcome scores. Healthcare resource use will be assessed by number of hospitalizations and emergency room visits. Physician and patient satisfaction with the treatment will also be determined. The total planned study duration is 48 months, with the main part being prospective, and retrospective data being collected for ≤12 months prior to start of pegcetacoplan. Results: Enrollment is expected to begin in Q3 2023 with the final report anticipated in Q1 2028. Summary/Conclusion: Pegcetacoplan is a newly approved, novel PNH therapy. This study aims to describe real-world usage and effectiveness of pegcetacoplan in PNH patients.Keywords: Paroxysmal nocturnal hemoglobinuria (PNH), Quality of life, Complement, Real world data